Klotho suppresses tumor progression via inhibiting IGF-1R signaling in T-cell lymphoma

Abstract

Klotho is a transmembrane protein and acts as an upstream modulator of insulin-like growth factor-1 receptor (IGF-1R) signaling, which was indicated to be involved in the pathogenesis of solid cancer and hematological malignancies, including T-cell lymphoma. Although Klotho was recently identified as a tumor suppressor in several types of human malignancies, the potential role of Klotho in T-cell lymphoma has not been reported. In the present study, we investigated the expression level and the molecular events of Klotho in T-cell lymphoma. Significantly lower expression of Klotho was observed in T-cell lymphoma patient samples compared to normal lymph nodes. Functional analysis after Klotho overexpression revealed significantly inhibited tumor cell viability in T-cell lymphoma. Moreover, apoptosis of T-cell lymphoma cells were induced after transfected with Klothooverexpressing vectors. Forced expression of Klotho resulted in decline of activation of IGF-1R signaling, accompanied by decreased phosphorylation of its downstream targets, including AKT and ERK1/2. These data indicated that Klotho acts as a tumor suppressor via inhibiting IGF-1R signaling, thus suppressing the viability and promoting apoptosis in T-cell lymphoma. Taken together, Klotho may serve as a potential target for the therapeutic intervention of T-cell lymphoma.